Orlando, Florida USA (UroToday.com) Andrea Necchi presented an exciting abstract at this year’s genitourinary cancer symposium expanding targeted therapy with use of daconatinib to penile squamous cell carcinoma. Patients with advanced disease and significant burden generally do poor in penile cancer. Therefore there is a need for further investigation in this rare disease. Dacomatinib is an irreversible TKI of human EGFR/HER1, HER2 and HER4. Necchi presented a phase 2 study (NCT01728233) of daconatinib (45mg daily) on patients with squamous cell histology, and clinical stage N2-3 or M1 disease and have not received prior chemotherapy.

In this phase II study, 26 patients were treated of which 77% had advanced disease with visceral or pelvic lymph node metastasis. Considering the high-risk group, a response was obtained in 30% over a follow up of 17 months. However, progression free survival and overall survival rates were 24% at 51%, respectively, at 1 year.

Tissue samples from 23 patients were analyzed post Daconatinib. Interestingly TERT mutations (60%) were found in responders only. Mutations were found in 47% of non-responders compared to 25% of responders. HRAS and BRAF mutations were common in the non-responders suggesting association with eGFR resistance.

The authors were able to conclude that Dacomitinib was active in HPV-negative, advanced penile squamous cell carcinoma. Among multiple altered pathways, we were able to delineate the possible molecular profile of responders. We look forward to the an expansion cohort to confirm the translational findings is planned. Clinical trial information: NCT01728233

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